[Research on a rational basis for the origin and treatment of arrhythmia]

Electrophysiological and pharmacological studies have revealed that the anti-arrhythmic drugs in use today possess one, or more than one, of four classes of action. 1) A direct action on the cardiac membrane, comparable to the action of local anaesthetics on nerve, which prevents the heart responding at a high frequency, by interfering with the entry of fast depolarising (sodium) current. 2) An anti-sympathetic action, achieved either by competition with adrenoceptors or by blockade of the release of noradrenaline. 3) An action on the phase of repolarisation, which delays the exit of outward current and so prolongs the absolute refractory period. 4) An action on the slow inward current, which reduces the secondary depolarisation (the "plateau") by calcium ions. Arrhythmias become more probable as a result of many different factors, and it is shown how each of the four classes of action can eliminate one of these arrhythmogenic factors, so that a rational explanation can be given for the mode of action of the various anti-arrhythmic drugs.